There are a large number of methods for producing amino acid based on the use of the microorganism.
For example, methods for producing L-phenylalanine are known, including those based on the use of recombinants of Escherichia coli (E. coli) as disclosed in Japanese Patent Publication No. 2-4276, Japanese Laid-Open Patent Publication (PCT) No. 4-501813, Japanese Laid-Open Patent Publication No. 5-244956, and International Publication WO87/00202.
Methods for producing L-phenylalanine or L-tyrosine are also known, including those based on the use of a mutant strain belonging to the genus Corynebacterium as disclosed in Japanese Laid-Open Patent Publication No. 61-128897, and those based on the use of a recombinant of Corynebacterium strain as disclosed in Japanese Laid-Open Patent Publication Nos. 60-34197, 60-24192, 61-260892, and 61-124375.
Methods for producing L-tryptophane have been reported, including those based on the use of a recombinant of Escherichia coli as disclosed in Japanese Laid-Open Patent Publication No. 57-71397 and U.S. Pat. No. 4,371,614, those based on the use of a mutant strain of Bacillus subtilis as disclosed in Japanese Patent Publication Nos. 53-39517 and 62-34399, those based on the use of a recombinant of Bacillus subtilis as disclosed in Japanese Laid-Open Patent Publication Nos. 61-104790 and 1-67179, those based on the use of a mutant strain belonging to the genus Brevibacterium as disclosed in Japanese Laid-Open Patent Publication No. 57-174096, and those based on the use of a recombinant belonging to the genus Brevibacterium as disclosed in Japanese Laid-Open Patent Publication No. 62-51980.
Methods for producing L-threonine have been reported, including those based on the use of a mutant strain belonging to the genus Escherichia as disclosed in Japanese Laid-Open Patent Publication No. 5-304969, those based on the use of a recombinant of Escherichia coli as disclosed in Japanese Patent Publication No. 1-29559, Japanese Laid-Open Patent Publication Nos. 2-109985 and 56-15696, and Japanese Laid-Open Patent Publication (PCT) No. 3-501682. Further, there have been reported those based on the use of a mutant strain of a bacterium belonging to the genus Corynebacterium as disclosed in Japanese Laid-Open Patent Publication No. 62-239996, and those based on the use of a recombinant bacterium belonging to the genus Corynebacterium as disclosed in Japanese Laid-Open Patent Publication No. 61-195695.
Methods for producing L-isoleucine have been reported, including those based on the use of Escherichia coli as disclosed in Japanese Laid-Open Patent Publication No. 5-130882, and those based on the use of a recombinant of Escherichia coli as disclosed in Japanese Laid-Open Patent Publication No. 2-458. Further, there have been reported those based on the use of a mutant strain of a bacterium belonging to the genus Corynebacterium as disclosed in Japanese Patent Publication No. 3-62395, and those based on the use of a recombinant belonging to the genus Corynebacterium as disclosed in Japanese Patent Publication No. 5-47196.
The microorganisms, which have been used in the methods for producing amino acid as described above, have been bred principally on the basis of the enhancement of enzymes for catalyzing reactions in common pathways for various amino acids and in inherent pathways subsequent thereto for individual amino acids, or on the basis of the avoidance of control effected by final products or the like (feedback inhibition and suppression). Specifically, those which have been employed for the breeding include, for example, addition of auxotrophy to the microorganism, addition of drug resistance, and amplification of enzyme genes concerning the biosynthesis system and introduction of mutation aimed at desensitization of control based on the recombinant DNA technique.
The enzyme, which is in charge of the first reaction in the common pathway of aromatic amino acid biosynthesis, is 3-deoxy-D-arabino-hepturonate-7-phosphate (DAHP) synthase (DS). DS of Escherichia coli includes three types of isozymes which are encoded by genes called aroF, aroG, and aroH respectively and which undergo feedback inhibition by L-tyrosine, L-phenylalanine, and L-tryptophane respectively. Concerning these genes, a technique for improving the productivity of aromatic amino acid is known, which is based on the introduction, into Escherichia coli, of a combination of a gene coding for a desensitized type enzyme (enzyme substantially not subjected to feedback inhibition) originating from aroF or aroG involving high enzyme activity and a tryptophane operon containing a gene coding for a desensitized type anthranilate synthase (AS) of the inherent system of L-tryptophane biosynthesis.
Phosphoenclpyruvic acid (hereinafter referred to as "PEP" and D-erythrose 4-phosphate (E4 P) are used as substrates in the synthetic reaction for DAHP. PEP also serves as precursors for biosynthesis of L-aspartic acid, L-threonine, L-isoleucine and the like. The substrates as described above are supplied from a carbon source such as glucose via the glycolytic pathway and the pentoses phosphate pathway. However, no case has been hitherto known in the breeding of amino acid-producing strains, in which the ability to supply such substrates is enhanced to improve the productivity of amino acid.
Phosphoenolpyruvate synthase (hereinafter abbreviated as "PPS" is an enzyme which is broadly found in the microorganism. This enzyme plays an important role to supply PEP from pyruvic acid in glyconeogenesis. Escherichia coli, which is a bacterium belonging to the genus Escherichia, has been used to perform cloning of a gene (pps) coding for PPS, determination of the nucleotide sequence of the gene, and functional analysis for the enzyme. Besides, it has been reported that DAHP is produced at a value approximate to the theoretical yield by means of simultaneous amplification of the pps gene and the transketorase gene in a dehydroquinate synthase-deficient strain (Patnaik, R. et al., Appl. Environ. Mircobiol., Vol. 60, No. 11, 3903-3908 (1994)). However, there has been known no case in which amplification of the pps gene enhances the productivity of aromatic amino acids and other amino acids.